Environ. Sci. Technol. 2005, 39, 3972-3980
Comparative Effects of Dietary Methylmercury on Gene Expression in Liver, Skeletal Muscle, and Brain of the Zebrafish (Danio rerio) P. GONZALEZ, Y. DOMINIQUE, J. C. MASSABUAU, A. BOUDOU, AND J. P. BOURDINEAUD* Laboratoire d’Ecophysiologie et Ecotoxicologie des Syste`mes Aquatiques (LEESA), Universite´ Bordeaux 1/UMR CNRS 5805, Place du Dr Peyneau, 33120 Arcachon, France
Effects of dietary methylmercury (MeHg) on gene expression were examined in three organs (liver, skeletal muscle, and brain) of the zebrafish (Danio rerio). Adult male fish were fed over 7, 21, and 63 days on three different diets: one control diet (C0: 0.08 µg of Hg g-1, dry wt) and two diets (C1 and C2) contaminated by MeHg at 5 and 13.5 µg of Hg g-1, dry wt. Total Hg and MeHg concentrations were determined in the three organs after each exposure duration, and a demethylation process was evidenced only in the liver. Thirteen genes known to be involved in antioxidant defenses, metal chelation, active efflux of organic compounds, mitochondrial metabolism, DNA repair, and apoptosis were investigated by quantitative real-time RTPCR and normalized according to actin gene expression. Surprisingly, no change in the expression levels of these genes was observed in contaminated brain samples, although this organ accumulated the highest mercury concentration (63.5 ( 4.4 µg g-1, dry wt after 63 days). This lack of genetic response could explain the high neurotoxicity of MeHg. coxI and cytoplasmic and mitochondrial sod gene expressions were induced early in skeletal muscle and later in liver, indicating an impact on the mitochondrial metabolism and production of reactive oxygen species. Results demonstrated that skeletal muscle was not only an important storage reservoir but was also affected by MeHg contamination. The expression of the metallothionein mt2 and the DNA repair rad51 genes was up-regulated in liver between 21 and 63 days, whereas in skeletal muscle, mt2 remained uninduced, and gadd and rad51 were found to be repressed.
Introduction Mercury (Hg) is a toxic metal used in a wide variety of applications; centuries of emissions of anthropogenic Hg have caused widespread environmental contamination over large regions of the globe (1). Mercury and more specifically methylmercury (MeHg) have been reported as hazardous environmental pollutants with severe risks for animal and human health (2, 3). Within aquatic systems, extremely low mercury concentrations are found in the dissolved water phase (
